Selecting Ions by Size in a Calcium Channel: The Ryanodine Receptor Case Study

AbstractMany calcium channels can distinguish between ions of the same charge but different size. For example, when cations are in direct competition with each other, the ryanodine receptor (RyR) calcium channel preferentially conducts smaller cations such as Li+ and Na+ over larger ones such as K+ and Cs+. Here, we analyze the physical basis for this preference using a previously established model of RyR permeation and selectivity. Like other calcium channels, RyR has four aspartate residues in its GGGIGDE selectivity filter. These aspartates have their terminal carboxyl group in the pore lumen, which take up much of the available space for permeating ions. We find that small ions are preferred by RyR because they can fit into this crowded environment more easily

Why do we need science-based co-creation?

For many years the transfer, exchange and collaboration of knowledge and technology between academia and industry have been discussed as an important means of generating commercial value. The underlying rationale for such collaborations is that knowledge and technology from academia lead to firms’ competitive advantage. What has received less attention in the literature, so far, is a science-based collaborative approach for addressing societal challenges. In particular, we focus on collaborations among different actors - ranging from academics, businesses, policy makers, intermediaries and society - who devote shared resources, competences and capabilities in developing unique solutions to economic and societal challenges. The specific domain of a such process - that demands thinking beyond the knowledge transfer or creation expected to produce business value - is framed as “co-creation”. This paper outlines a conceptual framework by capturing the heterogeneity of science-based co-creation and its determinants. In the paper, the concept of co-creation is positioned in the various strands of innovation literature which refer to collaboration across different domains, highlighting the uniqueness of co-creation. We suggest focussing on a distinctive character of co-creation: the production of both business value and social values that emerges with different forms of innovation, reach and prominence. While business value has its own metric in a monetary scale, when society is considered, metrics should refer to the many different dimensions that have been impacted on, leading to many social values (in plural). The paper highlights research gaps to further our knowledge on co-creation and suggests policy implications to support effective mutual interactions across science, technology and society

The dead end of classical innovation management and unsustainable innovation

• Sustainable innovation management via radical de-growth logic or incrementally.• Sustainable innovation management via pressure or voluntary ecosystem orientation. • Sustainable innovation management via formal processes.• Sustainable innovation management as a multilevel phenomenon

Conceptualizing the Innovation Process – Trends and Outlook

This paper introduces the evolving understanding and conceptualization of innovation process models. From the discussion of different approaches towards the innovation process understanding and modeling two types of approaches to the evolution of innovation models are developed and discussed. First the so-called innovation management approach which focuses on the evolution of the company innovation management strategies in different socioeconomic environments. Second is the analysis the evolution of innovation models themselves in conceptual sense (conceptual approach) as well as analysis of theoretical backgrounds and requirements for these models. The main focus of analysis in this approach is on advantages and disadvantages of different innovation models in their ability to describe the reality of innovation processes. The paper focuses on the advantages and disadvantages as well as potentials and limitations of the approaches and also proposes potential future developments of innovation models as well as the analysis of driving forces that underlie the evolution of innovation models recently

Selecting Ions by Size in a Calcium Channel: The Ryanodine Receptor Case Study

Many calcium channels can distinguish between ions of the same charge but different size. For example, when cations are in direct competition with each other, the ryanodine receptor (RyR) calcium channel preferentially conducts smaller cations such as Li+ and Na+ over larger ones such as K+ and Cs+. Here, we analyze the physical basis for this preference using a previously established model of RyR permeation and selectivity. Like other calcium channels, RyR has four aspartate residues in its GGGIGDE selectivity filter. These aspartates have their terminal carboxyl group in the pore lumen, which take up much of the available space for permeating ions. We find that small ions are preferred by RyR because they can fit into this crowded environment more easily

Species-specific and pathotype-specific binding of bacteria to zymogen granule membrane glycoprotein 2 (GP2)

With interest we read the paper by Juste et al 1 proposing the amount of zymogen-granule membrane glycoprotein 2 (GP2) on the surface of intestinal bacteria as a Crohn\u27s disease (CD) marker. Indeed, a decreased GP2 level was found on microbes in patients with CD as compared to those of healthy controls. GP2 is a homologue to the urinary Tamm–Horsefall protein demonstrating an antimicrobial function by binding type 1-fimbriated uropathogenic Escherichia coli (UPEC). Likewise, GP2 seems to interact with intestinal bacteria as a specific receptor of bacterial type-1 fimbriae (FimH) on intestinal microfold cells that are partaking in immune responses against such microbes.2 GP2 is overexpressed in the inflamed intestine of patients with CD and has an immunomodulating role in innate and acquired immune responses.3 ,4Interestingly, GP2 was identified as autoantigen of pancreatic antibodies in CD.4 Altogether, these findings indicate two major GP2 sources (pancreatic/intestinal) and support a role for GP2 in the interaction between the immune system and intestinal microbiota.3 Thus, loss of tolerance to GP2 could play a role in CD\u27s pathophysiology supposed to be exacerbated by preceding intestinal infections. In general, the findings by Juste et al 1 may be explained by a lower pancreatic GP2 secretion, an impaired GP2 binding to bacteria, or by a higher prevalence of bacteria with poor or no GP2 binding in patients with CD

A phoenix rising? The regeneration of the Ghana garment and textile industry

Some African countries’ premier industries, such as textiles, garments and agro-processing, which floundered in the face of market liberalization and stiff competition from cheap imports, are now going through regenerative changes, with some beginning to tell a cautionary tale of a leap upwards. Focusing on the Ghana garment and textile industry, we draw on a framework that integrates social practices and everyday general-purpose technologies to explore the rise, decline and regeneration of the industry. Explicating a fine analysis of how the performative reconfiguration of social practices and functional sources of innovation and technologies may combine to support innovation-driven growth, our study sheds light on how loosely connected actors within a hitherto floundering industry can learn to transform their situated practices to drive their ‘industrial regeneration’. Implications for the theory and practice of industrial regeneration are outlined

Probing the Role of Negatively Charged Amino Acid Residues in Ion Permeation of Skeletal Muscle Ryanodine Receptor

Sequence comparison suggests that the ryanodine receptors (RyRs) have pore architecture similar to that of the bacterial K+ channel KcsA. The lumenal loop linking the two most C-terminal transmembrane spanning segments in the RyRs has a predicted pore helix and an amino acid motif (GGGIG) similar to the selectivity filter (TVGYG) of KcsA identified by x-ray analysis. The RyRs have many negatively charged amino acid residues in the two regions linking the GGGIG motif and predicted pore helix with the two most C-terminal transmembrane spanning segments. We tested the role of these residues by generating single-site mutants, focusing on amino acid residues conserved among the mammalian RyRs. Replacement of two acidic residues immediately after the GGGIG motif in skeletal muscle ryanodine receptor (RyR1-D4899 and -E4900) with asparagine and glutamine profoundly affected ion permeation and selectivity. By comparison, mutagenesis of aspartate and glutamate residues in the putative linker regions showed a K+ conductance and selectivity for Ca2+ compared to K+ (PCa/PK) close to wild-type. The results show that the negatively charged carboxyl oxygens of D4899 and E4900 side chains are major determinants of RyR ion conductance and selectivity